The initiating pathologic change in acne vulgaris is the transformation of normal follicular epithelium of sebaceous follicles to a pattern of abnormal differentiation, resulting in the development of retention hyperkeratosis and comedones. Such blockage of the follicular ducts by retention hyperkeratosis is a prerequisite for the clinically more disturbing inflammatory lesions to develop. Our proposal is to elucidate the causative stimuli which induce retention hyperkeratosis in acne vulgaris, the cellular mechanisms whereby such a transformation is effected, and the metabolic and biosynthetic changes in the follicular epithelium which result from this transformation. We will use in vitro tissue cultures of follicular epithelial cells from ducts of sebaceous follicles to analyze the factors which affect the cellular kinetics and differentiation of these cells. We will analyze the changes in pilosebaceous cytochemistry and enzymatic activity during experimental comedo induction in rabbit ears in order to study the cellular mechanisms involved in the development of retention hyperkeratosis. Also, we will compare the changes in metabolic and biosynthetic activity of follicular epithelial cells from open comedones to that of uninvolved follicles in in vitro assays with radiolabeled substrates. We will evaluate the comedogenic potential of P. acnes in the rabbit ear bioassay, as well as in the human cutaneous bioassay for comedogenesis.